Tuberculosis (TB) is a contagious disease, which usually runs a protracted course, ending in death in majority of the cases, with relapse being a common feature of the disease. It is one of the most important causes of prolonged disability and chronic ill health. It is caused by the tubercle bacillus Mycobacterium tuberculosis, which is comparatively difficult to control. Drugs such as isoniazid, rifampicin, pyrazinamide, ethambutol streptomycin, para-aminosalisylic acid, ethionamide, cycloserine, capreomycin, kanamycin, thioacetazone etc. have been and are being currently used to treat TB. Amongst these, isoniazid, rifampicin, ethambutol and pyrazinamide are the first-line drugs of choice, which are administrated either as a single drug formulation or as a fixed-dose combination of two or more of the aforesaid drugs.
Even though, each of the abovementioned first-line drug regimen is highly effective for treatment of TB, however, they are associated with shortcomings, such as unpleasant side-effects and relatively long course of treatment. The later one results in non-compliance of the patient to the treatment leading often to failure of the treatment and most importantly, development of drug resistance. The development of drug resistance has long constituted a principal difficulty in treating human tuberculosis. The second-line drugs, on the other hand are less effective, more expensive and more toxic.
It is estimated that in the next twenty years over one billion people would be newly infected with TB, with 35 million people succumbing to the disease (WHO Fact Sheet No. 104, Global Alliance for TB Drug Development—Executive Summary of the Scientific Blueprint for TB Development: http://www.who.int/inf-fs/en/fact104.html). With the emergence of HIV related TB, the disease is assuming alarming proportions as one of the killer diseases in the world today.
A major thrust in research on antimycobacterials in the last decade has witnessed the development of new compounds for treatment of the disease,
a) differing widely in structures,
b) having different mode/mechanism of action,
c) possessing favourable pharmacokinetic properties,
d) which are safe and having low incidence of side-effects, and
e) which provide a cost-effective dosage regimen.
Several new class of compounds have been synthesized and tested for activity against Mycobacterium tuberculosis, the details of chemistry and biology of which could be found in a recent review by B. N. Roy et. al. in J. Ind. Chem. Soc., April 2002, 79, 320-335 and the references cited therein.
Substituted pyrrole derivatives constitute another class of compounds, which hold promise as antimycobacterial agents. The pyrrole derivatives which have been synthesized and tested for antitubercular as well as non-tubercular activity has been disclosed by:    a) D. Deidda et. al. in Antimicrob. Agents and Chemother., November 1998, 3035-3037. This article describes the inhibitory activity shown by one pyrrole compound, viz. BM 212 having the structure shown below, against both Mycobacterium tuberculosis including drug-resistant mycobacteria and some non-tuberculosis mycobacteria.
                The MIC value (μg/ml) against the M. tuberculosis strain 103471 exhibited by BM 212 was 0.70 as against 0.25 found for isoniazid.            b) M. Biava et. al. in J. Med. Chem. Res., 1999, 19-34 have reported the synthesis of several analogues of BM 212, having the general formula (The compounds disclosed by M. Biava et. al. in J. Med. Chem. Res., 1999, 19-34.) shown hereunder
                and the in vitro antimicrobial activity of the compounds against Candida albicans, Candida sp, Cryptococcus neoformans, Gram-positive or Gram-negative bacteria, isolates of pathogenic plant fungi, Herpes simplex virus, both HSV1 and HSV2, M. tuberculosis, M. smegmatis, M. marinum and M. avium.         However, the MIC values (μg/ml) of these compounds against the M. tuberculosis strain 103471 are found to be inferior to BM 212 and are in the range of 4-16.            c) M. Biava et. al. Bioorg. & Med. Chem. Lett., 1999, 9, 2983-2988. This article describes the synthesis of pyrrole compounds of formula (The compounds disclosed by M. Biava et. al. in Bioorg. & Med. Chem. Lett., 1999, 9, 2983-2988) shown hereunder
                and their respective in vitro activity against M. tuberculosis and non-tuberculosis species of mycobacteria.        However, the MIC values (μg/ml) of these compounds against the M. tuberculosis strain 103471 are found to be inferior to BM 212 and are in the range of 2-4.            d) F. Cerreto et. al. in Eur. J. Med. Chem., 1992, 27, 701-708 have reported the synthesis of certain 3-amino-1,5-diaryl-2-methylpyrrole derivatives and their in vitro anti-fungal activity against Candida albicans and Candida sp. However, there is no report on the activity of such compounds against M. tuberculosis.     e) C. Gillet et. al. in Eur. J. Med. Chem.-Chimica Therapeutica, March-April 1976, 11(2), 173-181 report the synthesis of several pyrrole derivatives useful as anti-inflammatory agents and as anti-allergants.    f) R. Ragno et. al., Bioorg. & Med. Chem., 2000, 8, 1423-1432. This article reports the synthesis and biological activity of several pyrrole derivatives as well as describes a structure activity relationship between the said pyrrole compounds and antimycobacterial activity. The compounds (The compounds disclosed by R. Rango et. al., Bioorg. & Med. Chem., 2000, 8, 1423-1432) synthesized and tested by the authors is summarized hereunder
                Y is H, CH3, OCH3, CH2, SO2, or a group of formula        
                wherein,        R is H, Cl, C2H5, or OCH3 and R1 is H, Cl, F, CH3, or NO2,        A is H or R        Z is a group of formula,        
                R2 is H, Cl, OH, or OCH3 and R3 is H or Cl        
None of the abovementioned disclosures report or suggest the in vivo efficacy including toxicity of any of the compounds described therein against experimental tuberculosis in animal model. Moreover, the higher MIC values of the compounds reported suggest that they may not be very effective in inhibition of Mycobacterium tuberculosis. 